Borrelia burgdorferi, the causative agent of Lyme disease, relies on a complex set of molecular mechanisms to survive in both tick vectors and mammalian hosts. Among its critical virulence factors is BB0323, a membrane-anchored protein essential for cell fission and pathogen persistence. This study reveals that BB0323 undergoes site-specific proteolytic cleavage at its C-terminus, yielding two distinct polypeptides: a larger N-terminal fragment and a smaller C-terminal fragment containing a conserved LysM domain. These processed forms are not merely degradation products but functional units with specialized roles in spirochete biology. The N-terminal polypeptide alone suffices to maintain normal cell morphology and support cell division, indicating that it carries the core structural and mechanical functions required for cytokinesis. In contrast, the C-terminal LysM-containing fragment, while dispensable for fission, is indispensable for successful infection in mammalian hosts. Despite its ability to bind peptidoglycan—a property consistent with known LysM domain function—the C-terminal fragment does not contribute detectably to cell wall remodeling or lytic activity. Instead, its role appears to be regulatory or signaling-related, possibly facilitating host-pathogen interactions during dissemination. The proteolytic processing of BB0323 is mediated by BbHtrA (BB0104), a periplasmic serine protease homologous to bacterial HtrA chaperone-proteases. This enzyme directly interacts with full-length BB0323 and cleaves it into the two mature fragments, suggesting a regulated maturation pathway. Notably, both polypeptides remain associated post-cleavage, forming a heteromeric complex that may stabilize the outer membrane or coordinate signaling events. The dependence of infectivity on this processed form underscores the importance of precise post-translational modification in B. burgdorferi pathogenesis. These findings highlight BB0323 as a central node in a multi-step regulatory system governing spirochete integrity and host adaptation.Brassicasterol manufacturer Targeting the proteolytic activation of BB0323 could offer a novel therapeutic strategy for disrupting Lyme disease progression without affecting host cells, as the process is specific to the pathogen’s unique physiology.9H-carbazole-2,7-dicarboxylic acid Autophagy Understanding how these polypeptides interact and regulate each other provides new insights into the intricate mechanisms underlying spirochetal cell division and persistence, advancing efforts to develop targeted interventions against one of the most widespread vector-borne diseases globally.PMID:34755897 MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com